Because of the richness of the information available from NMR, it has often been argued that NMR is the most powerful analytical technique for molecular structure determination. However, NMR has been more successful with liquids or materials dissolved in solvents than with rigid solids. The basic problem in NMR of solids is that rapid molecular tumbling and diffusion are not naturally present to average out chemical shift anisotropy and dipolar couplings of abundant spin nuclides. Hence, the lines are normally broad and unresolved (often hundreds of ppm in width). A large number of techniques have been developed to improve the resolution in NMR of solids, but most modern techniques include extremely rapid spinning of the sample at the “Magic Angle” (the zero of the second Legendre polynomial, 54.7°) with respect to B0. If the rotational rate is fast compared to chemical shift anisotropies and dipolar couplings (in units of Hz), the resolution is dramatically improved—often by two or three orders of magnitude. Even when the spinning is not fast enough to satisfy the above conditions, substantial improvements in resolution are generally obtained from the combination of MAS and multiple-pulse methods. Similar resolution problems are encountered in liquids of inhomogeneous systems, as in tissues and the mixtures of liquids and solids, because of susceptibility variations throughout the material. Here, relatively slow MAS is often effective in improving the spectral resolution of the liquid species by several orders of magnitude.
In U.S. Pat. No. 4,511,841, Bartuska discloses a modified Beams-type Bernoulli out-flow drive for MAS; and in his later U.S. Pat. No. 4,940,942, he discloses a method of improving its axial stability and providing variable temperature operation for the sample. In U.S. Pat. No. 5,508,615, I disclose a method of suppressing whirl instability in the radial bearings at very high surface speeds in MAS and improving the stability of balanced axial hydrostatic bearings, similar to the one used in U.S. Pat. No. 5,202,633. In a co-pending patent application (U.S. Publication No. 2006/0082371), I disclose a novel Bernoulli inflow axial bearing that is particularly advantageous for MAS when a ceramic dewar is required between the rotor and the sample coils.
The progress in increasing sensitivity in NMR has been impressive over the past five decades—three to five orders of magnitude, depending on the application. The most significant, generally applicable contribution to increasing the signal to noise ratio, S/N or SNR, in the past decade has been the introduction of cryoprobes for homogeneous liquid samples, such as that by Marek, U.S. Pat. No. 6,677,751 B1, in which the receiver coil, critical tuning elements, and preamps are cryogenically cooled while the sample is kept at some experimentally desired temperature, usually near room temperature (RT). Using high-purity aluminum coils and single-layer capacitors near 25 K with the preamps perhaps at 80 K, the S/N may be increased on one or more channels in a multi-resonant probe by typically a factor of three to four. The objective of this invention is to permit similar improvements in S/N in triple-resonance HR MAS NMR in high field magnets without cooling the sample, at least in wide-bore magnets.
Most modern NMR applications are directed at structure determinations of complex macromolecules, where it is often desirable to utilize a probe with high S/N at two or three different frequencies simultaneously, most often 1H/13C/15N, and perhaps additionally be able lock the field on the 2H resonance. RF circuit efficiencies in conventional 3 to 5 mm triple-resonance MAS probes with a single rf solenoid for signal reception at very high fields are typically in the range of 25-35% at the low-frequency (LF) and 15-40% at the mid-frequency (MF). For an example of a triple-resonance MAS circuit with a single sample solenoid, see my U.S. Pat. No. 5,424,645. Note that rf efficiency is usually defined as the percent of rf transmit power dissipated in the sample and the sample coil, as in principle other losses can be eliminated.
Significantly higher rf efficiencies on all channels in MAS have been achieved using a cross-coil for 1H and a solenoid for the MF and LF, as in my U.S. Pat. No. 6,130,537 or as discussed by Doty et al in “Magnetism in NMR Probe Design Part II: HR MAS,” in Concepts in Magn. Reson., Vol 10(4), 239-260, 1998. Still efficiencies are generally in the range of 30-50% for both the LF and the MF channels. Moreover, most advanced MAS NMR applications are now at 11.7 T (500 MHz) or higher and also are requiring magic angle gradient (MAG) coils, as disclosed by Cory in U.S. Pat. No. 5,872,452, and automatic sample change, all of which tend to push rf efficiencies toward the low ends of the above ranges.
Thus far, high-resolution (HR) NMR probes in which the sample coil and other circuit elements are at cryogenic temperatures have only been demonstrated for liquid samples in which the sample tube is aligned with the polarizing field, B0; and apparently in all prior CryoProbes, the sample coils are in an evacuated region for heat insulation reasons. Triple-resonance MAS probes in which both the sample and the sample coil may be simultaneously cooled to essentially the same temperature, both below 120 K, have been commercially available for high field magnets with 40 mm and larger RT shim bore for at least 15 years. In a few cases, cooling of the sample and sample coil to as low as 30 K has been possible in double-resonance MAS probes, but most critical tuning elements in such have not been cooled. Consequently, their gain in S/N has been limited.
While it is not difficult to achieve rf efficiency above 85% in single-tuned circuits, much lower efficiencies are always obtained in double- or triple-tuned circuits, especially for MAS probes, as noted above. The challenges are greater in MAS probes than in liquids probes partially because the circuits for solids NMR must also be designed to handle very high power, which requires larger circuit components and partially because it is often desirable to accommodate multinuclear tuning or one or more channels.
Using the same coil for both transmit and receive has been the preferred approach in NMR spectroscopy probes, both for liquids and solids, for at least three decades. In this case, Hoult's principle of reciprocity, which at least in its popular usage states that the NMR S/N during reception is, among other things, proportional to the square root of the circuit efficiency for generating a transverse rf magnetic field within the sample during transmit, has seldom been challenged.
Reciprocity, as defined above, fails to be valid when the various loss mechanisms (sample, sample coil, capacitors, shields, etc.) are at significantly different temperatures, as the transmit efficiencies are determined by the various resistances in the circuit, but the noise power during receive is proportional to both the resistance and its temperature. Hence, reciprocity fails in cryoprobes, such as that disclosed in U.S. Pat. No. 5,508,613, where the sample and perhaps some other minor loss components are much warmer than the sample coil. A co-pending application (U.S. Publication No. 2006/0152221), discloses another case in which reciprocity fails - when the sample coil is not cooled, but other critical circuit components are - that is practical in high field narrow bore magnets.
In the instant invention, the sample coil is also cooled, which permits considerably higher S/N but requires the use of a wide bore magnet, where the RT shim bore is typically 73 mm. The design is compatible with triple-resonance plus lock, MAG coils, extended-range variable temperature operation, automatic sample change, and commonly available closed-cycle cold fingers.